rs11570892

Positions:

• chr8-19966106-A-G
• chr8-19966106-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000237.3(LPL):​c.*796A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 151,740 control chromosomes in the GnomAD database, including 2,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2476 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150

Genes affected

LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-19966106-A-G is Benign according to our data. Variant chr8-19966106-A-G is described in ClinVar as [Benign]. Clinvar id is 362428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.*796A>G		3_prime_UTR_variant	10/10	ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.*796A>G		3_prime_UTR_variant	10/10		NM_000237.3	P1
LPL	ENST00000650478.1	c.*1047A>G		3_prime_UTR_variant, NMD_transcript_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26782 AN: 151626 Hom.: 2466 Cov.: 31

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.164

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.177 AC: 26820 AN: 151740 Hom.: 2476 Cov.: 31 AF XY: 0.176 AC XY: 13069 AN XY: 74090

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.166

Alfa AF: 0.160 Hom.: 3475

Bravo AF: 0.179

Asia WGS AF: 0.150 AC: 519 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperlipoproteinemia, type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11570892; hg19: chr8-19823617;